The synthesis and evaluation of a new class of amphiphilic molecules is proposed. The new compounds will contain polar and non-polar portions, as do all amphiphiles, but their conformational flexibility will allow them to present either a very polar or a very non-polar surface to the environment. These "conformational amphiphiles" will be designed so that when one set of surface elements is displayed, the other set, incompatible with the environment, can be sequestered internally. The ability of the new compounds to adjust surface polarity to match the polarity of the surrounding medium will depend upon long-range attractive non-covalent interactions. Structure-activity studies with conformational amphiphiles should, therefore, provide detailed mechanistic information on such interactions. The data from these studies will provide an important foundation for fundamental biochemical research because an understanding of what determines the strength of non-covalent associations, how molecules discriminate among potential binding partners and how environment affects these associations is a prerequisite for comprehension of the molecular basis of biological phenomena. The proposed research has medicinal applications in addition to its potential contributions to the study of biomolecule association. These applications derive from the novel phase transfer properties expected of conformational amphiphiles. The new amphiphiles should be able to move across barriers separating immiscible liquid layers (water and hexane for example) because of their Ability to alter surface polarity. Properly designed compounds might also be able to diffuse across biological membranes. Biomembranes function as barriers to unregulated movement of polar solutes from the environment into the cytoplasm; this barrier can be troublesome to medicinal chemists trying to get a drug substance form the bloodstream to an intracellular target (a particular enzyme, for example). The problem is particularly severe in delivering drugs across the blood- brain barrier. Conformational amphiphiles that can diffuse freely across biological membranes represent a potentially general solution to this problem.